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best ecommerce solution for a large business

What is the best shopping cart package for a large business? I'm thinking in terms of thousands of products and a fairly high volume of traffic. Normally I've used osCommerce or Virtuemart, but it was for smaller, Mom & Pop outfits.

I'm interested in both kinds of shopping carts, the hosted ones like 1shoppingcart as well as the ones installed locally like osCommerce.